Has the sponsor provided evidence from more than one adequate and well-controlled clinical investigation that supports the conclusion that ziprasidone is effective for the treatment of schizophrenia?

2. Has the sponsor provided evidence that ziprasidone is safe when used in the treatment of schizophrenia?

If the committee responds positively to the 2 general questions, there are some additional questions and issues that we would like you to consider in your discussions.

3. Do you think that ziprasidone’s risk of serious ventricular arrhythmias and SUD is greater than that of most other drugs in this class (even if that excess risk cannot be quantified)?

4. If you believe there is some excess risk, albeit unquantified, of serious ventricular arrhythmias and SUD associated with the use of ziprasidone, and you, nevertheless, conclude that ziprasidone should be approved, how should this excess risk be managed in labeling?

-First line vs second line status?

-What prominence should the risk be given in labeling?

-Black box warning

-Lesser warning statement

-Should there be a medication guide for patients to alert them to the risks of using ziprasidone?

5. Should the sponsor be required to conduct additional studies for ziprasidone, and when should these studies be conducted relative to any approval decisions regarding this application?

-Large comparative trial to estimate (or rule out at some level) the risk of excess SUD in association with the use of ziprasidone

-Study to demonstrate superior efficacy for ziprasidone, e.g., in patients demonstrated to be refractory to standard therapy